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The Journal of Neuroscience, March 1, 2002, 22(5):1592-1599
Therapeutic Effects of Coenzyme Q10 and Remacemide in Transgenic Mouse Models of Huntington's Disease
Robert J. Ferrante1, 2, Ole A. Andreassen3, Alpaslan Dedeoglu1, 2, Kimberly L. Ferrante5, Bruce G. Jenkins4, Steven M. Hersch6, and M. Flint Beal5 1 Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, Bedford, Massachusetts 01730, 2 Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, Massachusetts 02118, 3 Neurochemistry Laboratory, Neurology Service, and 4 Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, 5 Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, and 6 Center for Aging, Genetics and Neurodegeneration, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD. The combined treatment, using coenzyme Q10 and remacemide together, was more efficacious than either compound alone, resulting in a ~32 and 17% increase in survival in the R6/2 and N171-82Q mice, respectively. Magnetic resonance imaging showed that combined treatment significantly attenuated ventricular enlargement in vivo. These studies further implicate defective energy metabolism and excitotoxicity in the R6/2 and N171-82Q transgenic mouse models of HD and are of interest in comparison with the outcome of a recent clinical trial examining coenzyme Q10 and remacemide in HD patients.
Key words: Huntington's disease; excitotoxicity; coenzyme Q10; remacemide; mitochondria; transgenic
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251592-08$05.00/0
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